NYU Langone Health Med-Lit Review
Clinical Question: Does long-term beta-blocker therapy lower death or major adverse cardiovascular events in post-myocardial infarction (MI) patients with preserved (over 50%) or mildly reduced (40% to 49%) ejection fraction?
Background: Evidence for beta-blocker therapy post MI was established in the 1980s, before the introduction of coronary reperfusion therapy and contemporary secondary prevention strategies, including dual antiplatelet therapy and statins. Beta-blocker therapy is recommended for patients with MI and reduced ejection fraction (under 40%), but we have limited knowledge about the use of beta-blockers in patients with MI and preserved (over 50%) or only mildly reduced (40% to 49%) ejection fraction.
Study Design: Combining two separate studies, BETAMI and DANBLOCK, with an open-label, randomized, controlled trial with blind endpoint evaluation
Setting: Denmark and Norway
Synopsis: BETAMI-DANBLOCK trials were combined, and the decision to combine these trials was made four years before the end of the follow-up period. A total of 5,574 patients were randomized 1:1, with 2,783 patients receiving long-acting metoprolol at a starting dose of 50 mg (median dose), and 2,791 patients not receiving beta-blocker therapy. Median age was 63 years, 79.2% were men, 47.5% had ST-elevation MI, and 84.7% of the patients had a left ventricular ejection fraction of at least 50%. Both studies had similar inclusion and exclusion criteria: Recent MI (within 14 days), left ventricular ejection fraction of at least 40%, and no clinical evidence of heart failure. Almost all patients underwent coronary revascularization and received dual antiplatelet and statin therapy at discharge. The primary endpoint was a composite of death from any cause or major adverse cardiovascular events, including new MI, unplanned revascularization, ischemic stroke, heart failure, or malignant ventricular arrhythmias. After a median follow-up of 3.5 years, the primary endpoint occurred in 14.2% in the beta-blocker group and 16.3% in the no-beta-blocker group, with a hazard ratio of 0.85 (95% confidence interval [CI], 0.75 to 0.98). No significant difference was found in all-cause mortality, unplanned revascularization, or safety outcomes. New MI occurred in 5% of patients in the beta-blocker group compared to 6.7% in the no-beta-blocker group with a hazard ratio of 0.73 (95% CI, 0.59 to 0.92). Findings of this trial may not be generalized to other beta-blocker classes or higher doses.
Bottom Line: Beta-blocker therapy reduced the composite endpoint of death or major adverse cardiovascular events in patients post-MI with left ventricular ejection fraction over 40%, mostly by reduction in recurrent MI.
Citation: Munkhaugen J, et al. Beta-blockers after myocardial infarction in patients without heart failure. N Engl J Med. 2025;393(19):1901-1911. doi: 10.1056/NEJMoa2505985.
Video: View Dr. Modi’s video review.
Dr. Modi is a hospitalist in the department of medicine at the Veterans Affairs New York Harbor Health Care in New York and a clinical assistant professor with the department of medicine at NYU Grossman Long Island School of Medicine in Mineola, New York.